ABSTRACT
BACKGROUND: Pregnancy-associated breast cancer (PABC) is an aggressive disease, and since Chinese authority began to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. METHODS: Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled. Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. RESULTS: Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it's 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P < 0.001) as follows: in the PABC patients, Luminal B 38.4%, Triple negative breast cancer (TNBC) 30.1%, Human Epidermal Growth Factor Receptor 2 (HER-2) overexpression 15.8%, and Luminal A 10.8%; in the non-PABC patients, Luminal A 50.9%, Luminal B 20.1%, TNBC 17.4%, and HER-2 overexpression 8.0%. The 3-year disease free survival (DFS) of all PABC patients was 80.3%. The 3-year DFS of the patients in the first-pregnancy group was 78.4%, and that of the patients in the non-first-pregnancy group was 83.7% (P = 0.325). CONCLUSIONS: Our study proved that the proportion of women who developed PABC during the second or third pregnancy was extremely high relative to the newborn populations. The patients in the PABC population tended to present more luminal B and TNBC breast cancer than the non-PABC patients.
Subject(s)
Breast Neoplasms/mortality , Mastectomy/mortality , Pregnancy Complications, Neoplastic/mortality , Adult , Breast Neoplasms/epidemiology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Case-Control Studies , Female , Follow-Up Studies , Humans , Middle Aged , Pregnancy , Pregnancy Complications, Neoplastic/epidemiology , Pregnancy Complications, Neoplastic/metabolism , Pregnancy Complications, Neoplastic/pathology , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival Rate , Young AdultABSTRACT
BACKGROUND: The purpose of this study was to analyze the incidence and prognostic factors of patients with breast cancer liver metastases (BCLM) at initial diagnosis. METHODS: We utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with primary invasive breast cancer from 2010 to 2014. Multivariate logistic regression was conducted to determine factors associated with the presence of liver metastases upon initial diagnosis of breast cancer. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors in these patients. RESULTS: In total, 3,276 patients with liver metastases were identified upon initial diagnosis of breast cancer. Patients with hormone receptor-negative (HR-), human epidermal growth factor receptor 2-positive (HER2+) breast cancer had the highest incidence (4.6% among the entire population, 46.5% among the metastatic subgroup). Age, gender, race, pathological grade, extrahepatic metastases, tumor subtype, and marital status were identified as factors associated with the presence of liver metastases upon initial diagnosis of breast cancer. The median overall survival among the entire population with BCLM was 20.0 months. Patients with HR+/HER2+ breast cancer had the longest median survival of 36.0 months. The survival analyses indicated that older age, higher pathological grade, extrahepatic metastases, triple-negative subtype, unmarried status, and uninsured status were independent prognostic factors for a poorer prognosis. CONCLUSION: The study provides insight into the incidence and prognostic factors for patients with BCLM at initial diagnosis, which is important clinical information for risk evaluation and prognostic assessment.
ABSTRACT
Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in breast cancer development have not yet been elucidated. Using an in vivo CRISPR screen targeting RNA-binding proteins, we identified PHD finger protein 5A (PHF5A) as a key splicing factor involved in tumor progression. PHF5A expression was frequently upregulated in breast cancer and correlated with poor survival, and knockdown of PHF5A significantly suppressed cell proliferation, migration, and tumor formation. PHF5A was required for SF3b spliceosome stability and linked the complex to histones, and the PHF5A-SF3b complex modulated AS changes in apoptotic signaling. In addition, expression of a short truncated FAS-activated serine/threonine kinase (FASTK) protein was increased after PHF5A ablation and facilitated Fas-mediated apoptosis. This PHF5A-modulated FASTK-AS axis was widely present in breast cancer specimens, particularly those of the triple-negative subtype. Taken together, our findings reveal that PHF5A serves as an epigenetic suppressor of apoptosis and thus provides a mechanistic basis for breast cancer progression and may be a valuable therapeutic target.Significance: This study provides an epigenetic mechanistic basis for the aggressive biology of breast cancer and identifies a translatable therapeutic target. Cancer Res; 78(12); 3190-206. ©2018 AACR.
Subject(s)
Apoptosis/genetics , Breast Neoplasms/genetics , Carrier Proteins/metabolism , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Adult , Aged , Aged, 80 and over , Alternative Splicing/genetics , Animals , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carrier Proteins/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Female , Gene Knockdown Techniques , HEK293 Cells , Histones/genetics , Histones/metabolism , Humans , Mice , Middle Aged , Protein Serine-Threonine Kinases/metabolism , RNA Splicing Factors/metabolism , RNA-Binding Proteins , Signal Transduction/genetics , Spliceosomes/metabolism , Survival Analysis , Trans-Activators , Up-Regulation , Xenograft Model Antitumor AssaysABSTRACT
The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 µmol·L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity.
